Feenstra J, in't Veld B A, van der Linden P D, Grobbee D E, Stricker B H
Drug Safety Unit, Inspectorate for Health Care, Rijswijk, The Netherlands.
Br J Clin Pharmacol. 1998 Jul;46(1):71-7. doi: 10.1046/j.1365-2125.1998.00046.x.
In September 1995, the indication for the oral dopamine agonist ibopamine was restricted in the Netherlands and in several other European countries to patients with NYHA-class II heart failure as a result of an interim analysis of the PRIME-II trial. This trial demonstrated an increased risk of mortality in patients with NYHA-class III/IV heart failure on ibopamine. In September 1995, we initiated an assessment of the effects of ibopamine under everyday circumstances in a cohort of users of ibopamine in all NYHA-classes.
In a nationwide retrospective cohort study all 2147 community pharmacies and drug dispensing general practitioners received a request to list all patients to whom they had dispensed ibopamine in the preceding years. All responding drug dispensing outlets (DDO) received a questionnaire on cardiovascular risk factors and mortality for the general practitioner of a random sample of these patients. DDO were also requested to send an anonymised printout of the complete medication record. On the end-date of follow-up, February 15th 1996, mortality rates were compared across categories of ibopamine use, adjusted for potential confounders. To assess medication use, drug exposure was compared in a 3 months' period before date of death in the deceased, and before a random date in those patients who were still alive.
In patients with NYHA-class III/IV heart failure, multivariate analysis indicated that current use of ibopamine was significantly associated with mortality (RR 1.37;95% CI: 1.15-1.64). In patients with NYHA-class I/II heart failure, however, multivariate analysis showed a 2.03 (95% CI: 1.10-3.72) risk of mortality in current users of ibopamine. Apart from current use of ibopamine, male gender and increased serum creatinine were also independent risk factors for mortality in all NYHA-classes. No statistically significant association was found between mortality and current use of amiodarone or use of amiodarone at baseline.
The increased risk of mortality in patients with NYHA-class III and IV heart failure on ibopamine seems to confirm the main finding of the recently published PRIME-II trial. However, our results indicate that also patients with NYHA-class I/II heart failure may be at an increased risk of mortality when using ibopamine. Additional research on the effects of ibopamine in these patients is warranted and the use of ibopamine in NYHA-class II heart failure patients may have to be reconsidered.
1995年9月，由于对PRIME-II试验的中期分析，荷兰及其他几个欧洲国家将口服多巴胺激动剂异波帕胺的适应症限制为纽约心脏协会（NYHA）II级心力衰竭患者。该试验表明，服用异波帕胺的NYHA III/IV级心力衰竭患者死亡率增加。1995年9月，我们开始评估异波帕胺在日常情况下对所有NYHA分级的异波帕胺使用者队列的影响。
在一项全国性回顾性队列研究中，向所有2147家社区药房和配药全科医生发出请求，列出他们在前几年中给哪些患者配发过异波帕胺。所有回复的配药机构（DDO）收到一份关于这些患者随机样本的全科医生的心血管危险因素和死亡率的问卷。DDO还被要求发送完整用药记录的匿名打印件。在随访结束日期，即1996年2月15日，比较不同异波帕胺使用类别的死亡率，并对潜在混杂因素进行调整。为评估用药情况，比较了死者死亡日期前3个月以及仍存活患者随机日期前3个月的药物暴露情况。
在NYHA III/IV级心力衰竭患者中，多变量分析表明，当前使用异波帕胺与死亡率显著相关（相对危险度1.37；95%可信区间：1.15 - 1.64）。然而，在NYHA I/II级心力衰竭患者中，多变量分析显示当前使用异波帕胺的患者死亡率风险为2.03（95%可信区间：1.10 - 3.72）。除了当前使用异波帕胺外，男性性别和血清肌酐升高也是所有NYHA分级患者死亡的独立危险因素。未发现死亡率与当前使用胺碘酮或基线时使用胺碘酮之间存在统计学显著关联。
NYHA III级和IV级心力衰竭患者服用异波帕胺时死亡率增加，这似乎证实了最近发表的PRIME-II试验的主要发现。然而，我们的结果表明，NYHA I/II级心力衰竭患者使用异波帕胺时死亡率也可能增加。有必要对异波帕胺在这些患者中的作用进行进一步研究，并且可能需要重新考虑在NYHA II级心力衰竭患者中使用异波帕胺。
